Appl Health Econ Health Policy (2017) 15:85–93

DOI 10.1007/s40258-016-0272-z

ORIGINAL RESEARCH ARTICLE

Inflammatory Bowel Diseases (Crohńs Disease and Ulcerative

Colitis): Cost of Treatment in Serbia and the Implications
Marina Kostić1 • Ljiljan Djakovic2 • Raša Šujić2 • Brian Godman3,4,5 •

Slobodan M. Janković1

Published online: 1 September 2016

Ó The Author(s) 2016. This article is published with open access at Springerlink.com

Abstract Methods This cost-of-illness study was conducted to

Background Although the costs of treating inflammatory identify direct, indirect and out-of-pocket costs of treating
bowel disease (IBD) in developed countries are well patients with IBD in Serbia. Patients with IBD (n = 112)
established, they remain largely unknown in countries with completed a semi-structured questionnaire with data con-
recent histories of socio-economic transition including cerning their utilisation of heath-care resources and illness-
Serbia. related expenditures. All costs were calculated in Republic
Objective To estimate the costs of treatment including the of Serbia dinars (RSD) at a 1-year level (2014) and sub-
resources used by patients with IBD in Serbia from a sequently converted to Euros. Median values and ranges
societal perspective. This includes both Crohn’s disease were reported to avoid potential distortions associated with
and ulcerative colitis. mean costs.
Results Median total direct costs and total indirect costs
per patient per year in patients with Crohn’s disease were
Electronic supplementary material The online version of this 192,614.32RSD (€1602.97) and 28,014.00RSD (€233.13)
article (doi:10.1007/s40258-016-0272-z) contains supplementary and 142,267.15RSD (€1183.97) and 21,436.00RSD
material, which is available to authorized users.
(€178.39), respectively, in patients with ulcerative colitis.
& Brian Godman In both groups, the greatest component of direct costs was
Brian.Godman@ki.se hospitalisation.
Marina Kostić Conclusions Costs of IBD in Serbia are lower than in more
marrina2006kg@yahoo.com developed countries for two reasons. These include the fact
Ljiljan Djakovic that expensive biological therapy is currently under-utilised
ibd.srbija@gmail.com in Serbia and prices of health services are largely con-
Slobodan M. Janković trolled by the State at a low level. The under-utilisation of
slobnera@gmail.com biologicals may change with the advent of biosimilars at
1
increasingly lower prices.
Department of Pharmacology and Toxicology, Faculty of
Medical Sciences, University of Kragujevac, Kragujevac,
Serbia
2
Association of patients with Crohn’s disease and Ulcerative
colitis, Belgrade, Serbia
3
Division of Clinical Pharmacology, Karolinska Institute,
Karolinska University Hospital Huddinge, 141 86 Stockholm,
Sweden
4
Strathclyde Institute of Pharmacy and Biomedical Sciences,
University of Strathclyde, Glasgow G4 0RE, UK
5
Liverpool Health Economics Centre, Liverpool University,
Liverpool, UK
86
Key Points for Decision Makers
Cost-of-illness studies can provide useful
information in patients with chronic diseases in
countries with a recent history of socio-economic
transition including Serbia, which are still
economically challenged.
We performed a cost-of-illness study to identify key
direct, indirect and out-of-pocket costs of treatment
of patients with IBD and its complications to help
with future decision making in Serbia.
Total direct costs are lower in this study compared
with a number of other studies due to the limited
prescribing of biological therapies among patients
with IBD in Serbia.
Immunomodulatory therapy is an efficient
therapeutic strategy for IBD, but the prescribing of
these medicines is limited among Central and
Eastern Europe, including Serbia, due their current
high costs, prescribing restrictions and often high co-
payment levels.
This will change with increasing availability of
lower cost biosimilars starting with infliximab.
1 Introduction
Inflammatory bowel disease (IBD) is a clinical entity that
includes Crohn’s disease and ulcerative colitis. These are
chronic conditions with different clinical courses, which
affect the gastrointestinal system as well as other organs
including the skin, joints and eyes [1–3]. Currently the
aetiology of IBD remains unknown [2]. The clinical course
of Crohn’s disease and ulcerative colitis varies from an
asymptomatic phase to a very severe condition with
potentially fatal outcomes [1, 3]. The prevalence of these
chronic conditions has risen in Europe in recent years as
well as in other continents [4], and both diseases are
associated with high morbidity, reduced quality of life and
potentially considerable costs [5–8]; consequently their
management should be of interest to all key stakeholder
groups, including health authorities, physicians, patients
and patient associations.
The onset of Crohn’s disease and ulcerative colitis
occurs in the majority of cases during the most economi-
cally productive phase of a person’s life. Following this,
relapses and remissions occur through the remainder of a
patient’s life until they die.
M. Kostić et al.
Managing patients with inflammatory bowel disease
over the long term is associated with high costs, especially
when relapsing. This is because treatment at this stage of
the disease often includes hospitalisation, invasive diag-
nostic procedures, surgery and expensive biological
medicines including the anti-tumour necrosis factor (TNF)
alphas [9–12]. The chronic nature of IBD, and the frequent
inadequacy of patients’ responses to therapy if not ade-
quately managed, leads to increasing incidences of relapse,
which further increases the resource burden [10, 13].
Immunomodulatory therapy is an efficient therapeutic
strategy for IBD. However, due to its high costs and high
patient co-payments, its utilisation is often limited in
Central and Eastern European as well as less developed
countries. This is similar to the situation seen in the man-
agement of patients with rheumatoid arthritis [2, 14, 15].
This may change with the advent of the first biosimilars for
infliximab at considerably lower prices compared with the
parent compound [10, 16].
The economic impact of IBD has been recognised as
considerable in recent pharmacoeconomic literature
[7, 8, 17]. However, the real costs of treatment of Crohn’s
disease and ulcerative colitis within the Western Balkan
countries, with recent histories of socio-economic transi-
tions, remains ‘blurred’. This is because comprehensive
patient registries are still lacking, and many patients remain
untreated within state-owned health-care systems. Identi-
fying all relevant costs of IBD, and the factors which may
influence these costs, would provide comprehensive base-
line data for future pharmacoeconomic analyses and health
policy decisions among Balkan countries. Such studies
would help inform relevant stakeholders about the most
cost-effective treatment strategies for patients with IBD
within the Balkan countries with their limited resources
and growing health-care needs.
The aim of this study was to estimate the costs of
treatment and utilisation of resources among patients with
IBD (Crohn’s disease and ulcerative colitis) in Serbia
principally from a societal perspective. In addition, we
compared the costs of Crohn’s disease and costs of ulcer-
ative colitis in Serbia with other countries.
2 Material and Methods
This study was designed as a cost-of-illness study con-
ducted to identify direct, indirect and out-of-pocket costs of
treatment of patients with IBD and its complications.
2.1 Settings, Perspective and Questionnaire Design
A questionnaire design study was chosen because there was
no comprehensive patient level database including both
Cost of IBD in Serbia
hospital and ambulatory care, or register of IBD patients in
Serbia, at the time the study was conducted. This is still the
situation today, neither in written nor in electronic form. In
addition, recent studies have shown a good correlation
between self-reported health-care utilisation among
patients with IBD and their medical records [18]. Conse-
quently, we approached IBD patients via their association
for help with ascertaining key resource items using a
questionnaire methodology.
To help construct a robust questionnaire, we organised
several meetings with the President and Vice President of the
Patient Association. The objectives were to ascertain key
topics of the survey and to agree to the content and method-
ology. The final questionnaire was approved by the Associ-
ation and developed as a Word file. With the permission of the
main Board of the Serbian Association of Patients with
Crohn’s disease and Ulcerative Colitis, the word file was
subsequently uploaded onto the main Internet page of the
Association (see Electronic Supplementary Material). The
patients could subsequently download the file, complete the
questionnaire in their own time and on their own computers,
and send the completed questionnaire back to the Association
by e-mail. The responses were then entered manually onto an
Excel file, where descriptive statistics could be made.
The questionnaire was constructed in such a way as to
only collect data about health-care utilisation as well as
indirect and other costs including data of what patients had
actually spent for key items. There was no intention to
collect qualitative information such as knowledge about the
disease or attitudes to IBD, which would require additional
activities including potential scales and testing their relia-
bility and validity.
Since the association is active, and they communicate
with their members mainly via their official web site, we
thought patients would have enough skills and interest to
participate via an online questionnaire. The main board of
the Association also said they would discuss the ques-
tionnaire at their regular meetings to enhance the response
rate. This would include the main topics of survey and how
the questionnaire should be completed and returned. In this
way, the need to go to the public to seek IBD patients
willing to take part was negated, which we believed would
be both costly and very time consuming. Consequently in
agreement with the Association, we placed the question-
naire onto the main page of the Association.
Sampling was opportunistic, with the study population
comprising patients who suffer from IBD and who are
members of the Serbian Association of Patients with
Crohn’s disease and ulcerative colitis (n = 510).
Patients were offered the opportunity to complete the
questionnaire for 2 months during 2014 [19]. During this
period, 59 patients with Crohn’s disease (43 % male/57 %
female) and 53 patients with ulcerative colitis (46 % male/
87
54 % female) took part and completed the semi-structured
online questionnaire (see Electronic Supplementary Mate-
rial). There was no further selection process, with no
patient rejected from the subsequent analysis.
Patients subsequently entered their data anonymously
into the questionnaire. In this way, their identities were
protected.
We did not seek ethical approval. This is because our
survey did not include any interventions with patients, only
collecting and analysing data derived from IBD patients’
responses who voluntarily entered their data. For this type
of study in Serbia, we do not need ethics committee
approval. However, as mentioned, we obtained approval
from the Scientific Board of the Serbian Association of
Patients with Crohn’s disease and Ulcerative Colitis prior
to commencing this study and patients gave their informed
consent through actively completing the questionnaire.
This was entirely voluntary with no pressure placed on
patients to be part of the survey. In addition, no patient
received a financial reward for taking part.
As also mentioned, the data from patients was collected and
incorporated onto an Excel spreadsheet. The figures were
subsequently broken down into median values as well as
ranges. Median values were chosen for events and costs as
mean values could be distorted by outliers at either end of the
range. No statistical analyses were undertaken as we just
wanted to record the actual costs incurred by IBD patients with
either Crohn’s disease or ulcerative colitis in Serbia.
This study was performed from a societal perspective.
2.2 Demographic and Clinical Data
Demographic data included general information such as
patient’s age, sex, occupation, average monthly income and
lifestyle. Clinical data included information about the dis-
ease type (Crohn’s disease or ulcerative colitis), total
length of disease, stage of the disease and data about any
complications of the disease (surgery, colostomy and
others).
2.3 Costs
The questionnaire was structured in such a way as to enable
differentiation between direct, indirect and out-of-pocket
costs. Intangible costs could not be measured with this
questionnaire. Inpatient services were ascertained by
questions concerning the number of hospitalisations in the
last year, the ward type (intensive care or general type),
total length of hospitalisation in the last year and total
length of hospitalisation in the last 10 years. The questions
about outpatient services included: the number and type of
visits to physicians in the last year (visits to general prac-
tice and/ or specialists), the number of routine blood tests
88 M. Kostić et al.

in the last year, number of other blood tests (biochemistry) 3 Results

in the last year, the number of radiological and endoscopic
examinations in the last 5 years, the number of performed
biopsies in the last five years and the number of rehabili-
tation programs in the last 5 years including the average
length of any rehabilitation per program. Data about home
visits, home care, transport of the patients and disability-
related financial support received from Republic Fund for
Health Insurance (RFHI) were also included.
Indirect and out-of-pocket costs were obtained through
questions about lost wages for patients and their caregivers,
job losses of either the patient or caregiver due to IBD, the
costs for additional medical care, the costs of transport to-
and-from health care facilities and adjustments in the home
due to IBD. There were also questions about costs due to
physical rehabilitation, alternative and complementary
therapies, as well as over-the-counter medicines.
For the purpose of our study we used the official Tariff
book [20] of the Republic Fund for Health Insurance and
the prices from Official Gazette of Republic Serbia [21] to
estimate costs of medical services (Table 1). All costs were
collected as RSD. The consolidated costs were subse-
quently converted to Euros using the National Bank of
Serbia rate at April 2015.
Demographic and clinical characteristics of the patients
with Crohn’s disease and the patients with ulcerative colitis
are shown in Table 2.
Fifty-three patients with ulcerative colitis and 59
patients with Crohn’s disease took part (Table 1). The
median age was 36 (range 20–59) years for patients with
ulcerative colitis and 33 (range 13–55) years for patients
with Crohn’s disease. The median duration of disease was
7 (range 1–20) years for patients with ulcerative colitis and
8 (range 1–38) years for those with Crohn’s disease. None
of the patients with either ulcerative colitis or Crohn’s
disease received biological therapy (Table 2). The patients
with Crohn’s disease were maintained on azathioprine
2.5 mg/kg/day (100 % of patients), and the patients with
ulcerative colitis were also on azathioprine at 2 mg/kg/day
(100 % of patients).
Table 3 contains data on indirect and out-of-pocket
expenses of patients with either ulcerative colitis or
Crohn’s disease. These are typically recorded as median
costs and ranges. ’Other costs’ are shown without a range
since only three patients replied to this question, and they
all entered the same amount.

Table 1 Unit costs used in the study

Cost item Unit cost (RSD) References

Resection of intestines and restoring continuity (surgical intervention) 20,740.00 [20]

Day of hospitalisation: common care 1545.40 [20]
Day of hospitalisation: intensive care 1545.40 [20]
Visit to a general practitioner 192.11 [20]
Visit to a specialist physician 284.01 [20]
Full blood count 147.52 [20]
Set of biochemical analysis of blood: blood glucose, creatinine, AST, ALT 232.15, 235.15, 229.15, 229.15 respectively [20]
C-reactive protein and erythrocyte sedimentation rate 262.15, 43.70 respectively [20]
Chest X-ray 700.00 [20]
Computerised tomography of abdomen 6591.75 [20]
Nuclear magnetic resonance of abdomen 2552.38 [20]
Colonoscopy 6420.00 [20]
Colonoscopy with biopsy 6420.00 [20]
Physical therapy–one day in a hospital 1545.40 [20]
Disability-related financial support from the RFHI 16,105.09 [22]
Transport from home to health facility or reverse 256.79 [20]
Azathioprine 2.5 mg/kg/day for 2 months 4112.72 [21]
Infliximab, 100 mg 54,111.80 [21]
Adalimumab, 2 9 40 mg 94,497.30 [21]
Day out of work paid by the RFHI 1414.36 [20]
Average monthly wages in Serbia, August 2014 62,992.00 [22]
Cost of IBD in Serbia 89

Table 2 Demographic and clinical characteristics of the patients with inflammatory bowel disease who participated in the study
Variable Ulcerative colitis Crohn’s disease

Number of patients (male/female) 53 (25/28) 59 (25/34)

Age (median and range) 36 (20–59) 33 (13–55)
% of patients in employment 62 % 52 %
Median monthly income (RSD) and range 51,694.00 (10,000–170,000) 45,528.00 (10,000–95,000)
Duration of actual clinical state (months–median and range) 47 (4–240) 55 (2–96)
Duration of the disease (years)–median and range 7 (1–20) 8 (1–38)
% of patients with surgical interventions 8% 46 %
Surgical interventions in the last year (number per patient)–median and range 1 (1–2) 2 (1–10)
% of colostomies among operated patients 31 % 31 %
% of patients with complications 16 % 41 %
Total number of days spent in a hospital due to disease and its complications 34 (5–60) 31 (4–180)
in the last year (median and range)
Total number of days spent in an intensive care ward due to disease and its 4 (1–29) 21 (3–150)
complications in the last year (median and range)
Number of visits to general practitioners in the last year (median and range) 6 (1–30) 20 (1–200)
Number of visits to specialists in the last year (median and range) 5 (1–30) 11 (1–100)
Number of blood tests in the last year (median and range) 5 (1–23) 12 (1–30)
Number of other blood biochemistry analyses in the last year (median and 3 (1–10) 10 (1–30)
range)
Number of inflammatory markers tests in the last year (median and range) 2 (1–10) 8 (1–40)
Number of X-rays in the last 5 years (median and range) 3 (1–8) 5 (1–20)
Number of CT scan in the last 5 years (median and range) 2 (1–8) 3 (1–15)
Number of MRIs in the last 5 years (median and range) 2 (1–12) 2 (1–5)
Number of colonoscopies in the last 5 years (median and range) 3 (1–12) 3 (1–18)
Number of biopsies in the last 5 years (median and range) 2 (1–5) 3 (1–20)
Number of rehabilitation treatments in the last 5 years (median and range) 2 (1–5) 2 (1–10)
Median duration of a rehabilitation treatment in days and range 8 (7–15) 28 (10–150)
% of patients who were receiving the disability-related financial support from 0% 2%
RFHI
Percentage of patients transported to-and-from health-care facilities on 0% 3%
account of the RFHI

Table 4 contains data on the direct costs of surveyed 4 Discussion

patients with IBD in Serbia. Figure 1 contains details of the
consolidated median costs for patients with either Crohn’s We believe the costs of treating patients with ulcerative
disease or ulcerative colitis. colitis and Crohn’s disease in a West Balkan country (with
This showed that in Serbia, total median direct costs per recent history of socio-economic transition) have not been
patient per year in those with Crohn’s disease were previously reported in the literature. Our study contributes
167,973.9RSD (range 39,559.9–2,040,319.8RSD) [€1397.9 to the limited background knowledge to assist key stake-
(range €329.23–€16,980.02)] and total indirect costs per holders in the Balkans in their future decision making,
patient per year were 28,014.00RSD (range which is a demanding task within limited health-care
3000.00–81,000.00RSD) [€233.1 (range €24.9–€674.1)] budgets and a rising incidence of IBD. Economic analyses
(Fig. 1). Total direct costs per patient per year in those with of chronic diseases are crucial to help provide clear insight
ulcerative colitis were 122,526.0RSD (range into the extent of direct and indirect costs and their impact
49,037.9–761,916.3RSD) [€1019.6 (range €408.1– on national health-care budgets. This is especially the case
€6340.8)] and total indirect costs per patient per year were for IBD in view of the potential impact on indirect costs
21,436RSD (range 3500–68,000RSD) [€178.3 (range due to disability and decreased work productivity. How-
€29.1–€565.9)]. ever, we are aware different authorities throughout Europe
90 M. Kostić et al.

Table 3 Nature of indirect and out-of-pocket costs of treating patients with inflammatory bowel disease including median values and ranges
Variable Ulcerative colitis Crohn’s disease

Number of days of absence from work due to illness in the last year (median) 8 (1–60) 33 (1–365)
% of patients who lost their job due to illness 31 % 25 %
Duration of unemployment in years 3 (1–20) 4 (1–23)
% of patients with caregivers within the family 44 % 64 %
Median working hours of caregivers per day 8 (1–24) 8 (1–24)
Median number of days with lost wages of caregivers 4 (1–30) 84 (5–365)
% of caregivers who were not employed due to illness of a family member 16 % 13 %
Median duration of unemployment of caregivers in years 4 (3–10) 6 (2–30)
% of patients with paid caregivers (not family members) 0% 3%
% of patients with home adjustments due to the illness 10 % 11 %
Median monthly costs of transport due to illness (RSD) 2343 (500–9000) 2632 (500–10,000)
Median monthly costs due to special kind of nutrition because of the illness (RSD) 11,026 (1000–40,000) 13,009 (1000–25,000)
Median monthly costs due to alternative or complementary therapy (RSD) 3976 (1500–10,000) 8382 (1000–38,000)
Other costs (RSD) 4000 4000

Table 4 Costs per patient from medical services including medicines in RSD (median and range)
Type of medical service Costs of ulcerative colitis Costs of Crohn’s disease per
per patient patient

Visits to general practitioner in the last year 1121.8 (186.9–5609.4) 3739.6 (186.9–37,396.0)
Visits to a specialist in the last year 934.9 (186.9–5609.4) 2056.7 (186.98–18,698.0)
Complete blood count in the last year 737.6 (147.52–3392.9) 1770.2 (147.5–4425.6)
Blood biochemistry in the last year 11,901.1 (3967.0–39,670.6) 39,670.6 (3967.0–119,011.8)
Markers of inflammation in the last year of the disease 3233.1 (1616.5–16,165.7) 12,932. 5 (1616.5–64,662.8)
X-rays in the last 5 years 1892.13 (630.7–5045.6) 3153.5 (630.71–12,614.2)
CT scans in the last 5 years 13,183.5 (6591.7–52,734) 19,775.2 (6591.7–98,875.5)
MRIs in the last 5 years 5104.7 (2552.3–30,628.5) 5104.7 (2552.3–12,761.9)
Colonoscopies in the last 5 years 6420 (2140–25,680) 6420 (2140–38,520)
Biopsies in the last 5 years 9880 (4940–24,700) 14,820 (4940–98,800)
Rehabilitation treatment in the last 5 years 2300 (1150–5750) 2300 (1150–11,500)
Total costs of hospitalisations due to the disease and its complications in the 52,350 (7725–92,700) 47,895 (6180–278,100)
last year
Total costs of hospitalisation in intensive care ward due to the disease and its 6180 (1545–44,850) 32,445 (4635-231,750)
complications in the last year
Costs of medication per year, estimated by the average dose of medicines 19,741.0 24,676.3
taken by the patient and their list price in the Official Gazette

use different cost components in their reimbursement and
funding decision making [23].
These costs (see Fig. 1) are lower than those seen in some
other countries. For example, the direct costs of treating
ulcerative colitis in Germany and the UK were estimated as
GB£3021 (€3871.0) per patient per year, whilst treating
Crohn’s disease cost was GB£3416 (€4377.1) per patient per
year; with half of the costs due to hospitalisation and surgery
[24]. The results from a study conducted in patients from
across Europe and Israel showed that the mean total costs per
patient per year were higher in patients with Crohn’s disease
at €2548 compared with an estimated total cost of €1524 for
patients with ulcerative colitis, which was similar to our
findings. The highest total costs per patient-year were
recorded in Denmark at €3705, and the lowest in Norway at
€888 [24]. Kappelman et al. [25] showed that the mean
annual costs per patient are considerably higher in the USA
than in Europe. This is because total annual direct costs were
Cost of IBD in Serbia
Total direct costs
for Crohn's
disease per
paent per year
167,973.9
Total direct costs
for ulcerave
collis per paent
per year
122,526
Total indirect
costs for Crohn's
disease per
ulcerave collis
paent per year
28,014
Fig. 1 Total median annual costs (direct and indirect) per patient
with ulcerative colitis and Crohn’s disease in RSD
US$8265 (€7429.9) per patient with Crohn’s disease and
US$5066 (€4554.1) per patient with ulcerative colitis.
Due to the chronic and progressive clinical course of
IBD, we had expected a greater impact of indirect costs due
to disability and decreased work productivity since the onset
of IBD is mostly during the economically productive phase
of an adult’s life. As a result, there should be appreciable
indirect costs due to lost wages, work disability and early
retirement in view of its relapsing and remitting nature.
However, this was not found to be the case in our study.
Surgical treatment of IBD is a therapeutic option for
those patients with severe Crohn’s disease and in those
patients with ulcerative colitis where the response to
medical treatment is inadequate [24]. In our study, the
percent of patients undergoing surgical interventions were
8 % in those with ulcerative colitis and 46 % in those with
Crohn’s disease, while 31 % of operated patients in both
groups had a colostomy. These findings are similar to those
from other European countries where patients with Crohn’s
disease who experienced surgery and colostomy were 37 %
among East European countries, 38 % in Norway, 50 % in
Sweden, 61 % in Denmark and 52 % in Hungary. In
patients with ulcerative colitis, surgery and colostomy rates
were 8.7 % in East European countries, 9.8 % in Norway,
24 % in Denmark and 2.8 % in Hungary [24]. The risk of
91
surgery and colostomy is lower today compared to the rates
reported in studies prior to 1990 [24, 25]. This is due to a
restrictive policy toward surgical procedures and the
introduction of potent medical treatments such as the bio-
logical drugs [24].
Admission to hospital and the duration of treatment are
mostly determined by local health-care policies and it is
difficult to compare these parameters across European
countries. For example, in some studies the average dura-
tion of hospitalisation for IBD patients was estimated at
10 days [24, 26]. Similar findings were obtained from the
study of Bassi et al. [2] where patients with ulcerative
colitis and Crohn’s disease lost 17 and 20 days from work
during 6 months, respectively. The results of our study
(Table 2) indicate that the duration of hospitalisation was
longer, with a median of 31 days in those with ulcerative
colitis and 34 days in those with Crohn’s disease.
Total indirect Loss of function and the ability to fully engage in work
costs for
and other activities is a serious consequence of IBD. This
per paent per will negatively affect both patients’ income and their quality
year of life [24]. Unemployment and underemployment among
21,436
patients with IBD has been the subject of many studies in
Europe, Canada and United States [24, 27–29]. The reduc-
tion in working ability in patients with IBD reported in these
studies ranged from 3 to 13 %, mostly in patients with
ulcerative colitis (about 60 % of all patients with reduced
working ability) [17, 24, 28, 29]. In our study, 31 % of
patients with ulcerative colitis lost his/her job due to illness,
with a median duration of unemployment of 3 years.
Twenty-five percent of patients with Crohn’s disease lost
his/her job due to illness, with a median duration of unem-
ployment of 4 years. A reduction of working ability nega-
tively correlates with the quality of life of these patients, and
produces appreciable economic losses due to lost wages,
decreased productivity and early retirement [24]. However,
in our study (Table 3) only 2 % of patients with Crohn’s
disease received disability pensions. This may be one of the
key factors for lower than envisaged indirect costs in our
study. This compares with a Norwegian population where
19 % of patients with IBD 10 years after diagnosis received
a disability pension [28]. We accept that the ability of
countries to provide income assistance programmes for IBD
and other patients varies among European countries. This
primarily depends on the economic welfare and health-care
polices of these countries. We also accept that wages are
appreciably lower in Serbia than among Western countries,
which will also affect the level of indirect costs.
Since IBD also affects the ability of patients to under-
take everyday activities, patients may need assistance,
which is provided by caregivers. In the recent literature, it
has been estimated that caregivers spend on average 30
hours per week with patients with inflammatory bowel
disease [28]. In our study (Table 3), the median number of
92
hours that a caregiver spent with both groups of patients
was 56 per week. The median duration of unemployment of
patients was 4 years in those with ulcerative colitis and
6 years in those with Crohn’s disease. However, we
recognise that this was a selected population with increased
likelihood of having more severe disease than the average
of all patients with IBD in Serbia. However, this did not
always translate into indirect costs as seen by lower than
expected figures (Fig. 1).
The out-of-pocket expenses include costs due to
housekeeping or modifications to the home due to illness,
special nutritional products and complementary and alter-
native medicines [28]. These costs per patient-year in our
study were estimated at 28,014 RSD (€233.13) in those
with ulcerative colitis and 21,436RSD (€178.39) in those
with Crohn’s disease. In the UK, these costs were lower in
patients with IBD at approximately £80 (€102.5) per
patient and £132 (€169.1) per patient for ulcerative colitis
and Crohn’s disease, respectively [2].
Overall our study indicates that patients with ulcerative
colitis and Crohn’s disease from a Western Balkan country
are comparable with those in other European countries in
many socio-economic regards. However, biological ther-
apy is currently under-utilised in Serbia in comparison to
Western European countries as seen by the fact that none of
the patients in this study were on biological therapies.
Other studies have also shown the low use of biological
therapies in immunological diseases among Central and
Eastern European countries compared to Western Euro-
pean counties, enhanced by restrictions, high co-payments
and a lack of reimbursement [10, 15]. Whilst this decreases
direct medical costs due to lower drug acquisition costs,
this can increase hospitalisation costs as well as indirect
costs due to work absenteeism.
The next stage of our research will be to estimate the
cost-effectiveness of biological medicines on total costs,
building on our comprehensive catalogue of actual
resource consumption. The case for the biological
medicines and their cost-effectiveness has been demon-
strated in a number of countries and studies [11, 12]. The
case of improving patient care in a cost-efficient manner
should be strengthened by the availability of biosimilars.
For example, infliximab is now available at approximately
30 % of the price of the originator in Norway [16], with a
recent study demonstrating the potential for considerable
savings with the biosimilar infliximab in patients with
Crohn’s disease among a number of Central and Eastern
European countries [8]. There have been concerns about
the effectiveness and safety of biosimilar infliximab.
However, ongoing studies in patients in Central, Eastern
and Western European countries as well as South Korea are
showing that biosimilar infliximab is effective and well
tolerated [8, 16, 30]. This provides hope for the future.
M. Kostić et al.
We accept that a major limitation of this study is the
selection of patients for costing purposes. We undertook
this approach, with its inherent selection bias due to the
need for online access and computer literacy, as the most
efficient way of contacting patients with IBD. We also
acknowledge a low response rate (22 %). This low rate was
not expected since the Association is active and in regular
contact with its members via electronic and other means.
We must acknowledge this low sample size, which limits
the representativeness and generalisability of the study
findings. We also accept that our survey involved the
reporting of all medical examinations and other key events
over a 5-year period, which could generate recall bias.
However, as stated earlier, recent studies have shown a
good correlation between self-reported health-care utilisa-
tion among patients with IBD and their medical records
[18]. Despite these limitations, we believe our findings are
a good start to addressing the lack of information regarding
current resource utilisation among patients with IBD in
countries such as Serbia.
We have also sought to address some of the concerns
with studies such as cost-of-illness studies and budget
impact analysis [31] by using patient-level data, local
costings and avoiding conflicts of interest. We acknowl-
edge though that we did not check the accuracy of
respondent answers. However, we would not expect these
to be falsified as it is in the interest of these patients to
accurately record the resources they consume as far as they
are able to.
In conclusion, we believe we have documented the total
costs of treating patients with IBD in a Balkan country,
adding to the literature for Western European countries.
This is particularly important for countries similar to Serbia
with their recent socio-economic history. We also believe
that this study provides important insight for all key
stakeholder groups in the future to help shape future policy
decisions. We will be building on the findings.
Author contributions Marina Kostić contributed to the study design,
collection of data, statistical analysis and writing of the manuscript.
Ljiljan Djakovic contributed to the study design, collection of data
and statistical analysis. Raša Šujić contributed to the study design,
preparing the online questionnaire, collection of data and statistical
analysis. Brian Godman contributed to the study design and the
writing of the manuscript. Slobodan M. Janković contributed to the
study design, collection of the data, preparing the online question-
naire, statistical analysis and the writing of the manuscript.
Compliance with Ethical Standards
This study was partially funded by Grant No. 175007 given by the
Serbian Ministry of Education. The authors Brian Godman, Marina
Kostić, Ljiljan Djakovic, Slobodan M Janković and Raša Šujić have
no conflict sof interest in regard to this article, although two of the
authors (LD and RS) are members of the Association of Patients with
Crohn’s Disease and Ulcerative Colitis.
Cost of IBD in Serbia
Approval from the Scientific Board of the Serbian Association of
Patients with Crohn’s disease and Ulcerative Colitis was obtained
prior to commencing this study. The study was performed in accor-
dance with the ethical standards of the Declaration of Helsinki.
Informed consent was obtained from all individual participants
included in the study by the very nature of data collection.
Open Access This article is distributed under the terms of the
Creative Commons Attribution-NonCommercial 4.0 International
License (http://creativecommons.org/licenses/by-nc/4.0/), which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided you give appropriate credit to the original
author(s) and the source, provide a link to the Creative Commons
license, and indicate if changes were made.
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